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PROVENANCE_all

rg78803 edited this page Sep 6, 2026 · 1 revision

Corpus β€” every guide RNA the registry publishes

The first version of this screen carried two guides, found by searching NCATS GSRS for drug names recalled from memory. That is a completeness defect no harness can catch: a guide nobody recalls is silently absent from a safety map. The registry is enumerated instead.

How the guides were found

All 742 substances of class nucleicAcid were fetched from GSRS and scanned for the canonical SpCas9 sgRNA scaffold GUUUUAGAGCUAGAAAUAGCAAGU. Fifteen carry it. In every one the scaffold begins at position 20, so the spacer is the preceding 20 bases β€” which is what makes the 20-base reading a measurement rather than a convention.

Finding them by structure rather than by name recovered guides that a name search missed, and it vindicated an earlier refusal rather than overturning it. NTLA-2001's own record is the full 4,423-base molecule carrying the Cas9 messenger RNA, with no isolatable spacer, and it was refused. Its guide exists under a separate record β€” Nexiguran, UNII 5G537B4BTJ β€” and the enumeration found it. Refusing to guess at the mRNA record lost nothing.

The cut site is measured, not declared

Most guide records carry no target annotation, so requiring a declared target chromosome cannot enumerate a registry. A guide's measured cut site is where its zero-mismatch match actually falls in the assembly. Off-targets are the sites outside it. A guide with no zero-mismatch site anywhere gets no off-target list, because its published spacer and the assembly disagree.

The assembly

GENCODE GRCh38 primary assembly, sha256 b760d18dbb651dd14dfc290083371b3ef3bff122d43a9cefb13ca4ecf38f05ca, 3,099,750,718 bases across 194 sequences. Pinned by URL and digest rather than committed.

🧬 CURES β€” read in this order

Each step is the reason the next one exists. Nothing here is medical advice, and no page calls any medicine safe or unsafe.

1 Β· Why an exact safety screen at all

2 Β· The three libraries, which grow rather than close

3 Β· The maps β€” every place a molecule could act, counted

4 Β· One medicine at a time

  • Zilganersen β€” the first treatment for Alexander disease, screened on the real approved sequence
  • A drug an AI designed β€” rentosertib for pulmonary fibrosis, and exactly what our instruments reach
  • CAR-T, halted β€” the verdict a regulator could re-derive
  • N-of-1 antisense β€” the only safety net at a population of one
  • VERVE-102 β€” the off-target lattice a stranger can re-derive
  • PM359 β€” prime editing, certified before anyone is dosed
  • Del-Zota β€” the one safety question that can be made exact

5 Β· What keeps a disease alive, and what moves it

βš–οΈ How to read any page here

πŸ”¬ The method β€” exact against float, domain by domain

The same move every time: take a domain where a floating-point model is the accepted instrument, compute the same quantity in exact integers, and seal the cases where the two render opposite verdicts. The subject under grading is always the instrument, never the phenomenon.

⚑ Fusion β€” the energy case

🌍 The planet, and the sky

πŸ› Markets, money and risk

βš›οΈ Run a court yourself

πŸ“’ Program ledger β€” every study by lifecycle

A study appears here under the state its evidence has earned, and above under the question it answers. The two are different filings of the same work, on purpose.

βœ… LAW FROZEN Β· DATA SEALED

πŸ”΄ LIVE CLAIM β€” standing, not sealed

🌊 CHARTER Β· OPEN β€” the findings, published either way

β˜€οΈπŸŒ‘ Eclipse 2026 β€” Study 01, DATA SEALED

πŸ”¬ Discoveries and flows

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